Volume 41 Issue 6, June 2009

Five genome-wide association studies of the timing of menarche and menopause have now taken us beyond the range of candidate gene and linkage studies. The list of new genetic associations identified for these two traits should shed light on the mechanisms of ovarian aging, as well as breast cancer and other diseases associated with reproductive lifespan.

Tubulins are key structural components of all cells. A new study reveals roles in brain development for a specific β-tubulin isoform and highlights potential for functional diversity in the β-tubulin gene family.

The etiology of the sleep disorder narcolepsy has not been firmly established, although an autoimmune pathogenesis has been proposed and is supported by a strong genetic association with the HLA. A new genome-wide association study provides further support for the autoimmune basis of narcolepsy by uncovering a robust association at the T-cell receptor alpha locus.

André Uitterlinden and colleagues report a genome-wide association study for age at natural menopause, from the Rotterdam Study and TwinsUK, with replication in additional cohorts. They report three loci associated with age at natural menopause, which is a known risk factor for several cancers, osteoporosis and cardiovascular disease.

André Uitterlinden and colleagues report loci at 9q31.2 and LIN28B associated with age at menarche from a meta-analysis of genome-wide association studies including 17,510 females from eight different population-based cohorts.

Mark Samuels and colleagues report the identification of mutations in mitochondrial carrier family member SLC25A38 in nonsyndromic autosomal recessive congenital sideroblastic anemia.

Massimo Zeviani and colleagues identify a factor, called SDHAF1, required for assembly of the mitochondrial succinate dehydrogenase ubiquinone reductase complex by conducting a genetic analysis of two families segregating a rare, progressive leukoencephalopathy.

Dominic Kwiatkowski and colleagues of the MalariaGEN and the WTCCC consortiums report a genome-wide analysis of severe malaria in The Gambia. They provide guidance for design of GWAS in African populations, and demonstrate the usefulness of multipoint imputation based on population-specific sequencing data.

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension.

Daniel Levy and colleagues report a meta-analysis of genome-wide association studies for blood pressure traits as part of the CHARGE consortium, reporting eight loci with replicated association to systolic and/or diastolic blood pressure, with one of these loci also associated to hypertension.

Shizufumi Ebihara and colleagues report the identification of Usp46 as a quantitative trait gene underlying mouse behavior in the tail suspension and forced swimming tests, which are widely used for assessing depression-like behavior. Usp46 encodes a ubiquitin-specific peptidase.

Gunter Reuter and colleagues show that the cytosine-5 methyltransferase DNMT2 controls retrotransposon silencing and telomere integrity in somatic cells of Drosophila.

Patrick Concannon and colleagues present a type 1 diabetes genome-wide association study and meta-analysis in 7,514 cases and 9,045 reference samples, reporting 22 newly identified loci.

Emmanuel Mignot and colleagues report that variants in the T-cell receptor alpha (TRA@) locus are strongly associated with narcolepsy. This is the first documented involvement of the TCR locus in human disease and will shed light on how HLA-TCR interactions contribute to organ-specific autoimmune targeting.

Caroline Fox and colleagues report results of a genome-wide association study to identify common variants associated with indices of renal function. They show that variants at UMOD, a gene previously implicated in rare monogenic forms of kidney disease, are associated with risk of chronic kidney disease in the general population.

John Maris and colleagues report results of a genome-wide association and replication study for aggressive neuroblastoma. They show that common variants in the BARD1 locus at 2q35 are strongly associated with the disease.

Chunyan He and colleagues report genome-wide association studies for both age at menarche and age at natural menopause from the Nurses Health Study and the Women's Genome Health Study.

Ken Ong and colleagues report a genome-wide association study for age at menarche. They find LIN28B associated with age at menarche, as well as several traits related to onset of puberty in both females and males.

Patrick Sulem and colleagues report a genome-wide association study of age at menarche, finding and replicating an association with LIN28B. The authors test a number of variants previously associated with height and BMI and find that five loci previously associated with BMI are also associated with age at menarche.

Nicholas Katsanis and colleagues report that a common allele of RPGRIP1L is associated with photoreceptor loss in ciliopathies. An A229T variant in RPGRIP1L compromises binding to RPGR and modifies the retinal degeneration phenotype in ciliopathies caused by mutations in other genes.

Jamel Chelly and colleagues report that de novo mutations in TUBB2B, encoding a β-tubulin, are associated with asymmetrical polymicrogyria and other brain malformations. They also show that in utero knockdown of Tubb2b in rat results in defective neuronal migration.

Zsuzsanna Izsvák and colleagues report the generation of a hyperactive version of the Sleeping Beauty transposase that supports efficient and stable gene transfer into human CD34⁺ cells enriched for hematopoietic stem or progenitor cells.